{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:57:10Z","timestamp":1789952230973,"version":"4.0.1"},"reference-count":53,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2018,7]]},"abstract":"\n Background<\/jats:bold>\n Steroid-sensitive nephrotic syndrome (SSNS) is a childhood disease with unclear pathophysiology and genetic architecture. We investigated the genomic basis of SSNS in children recruited in Europe and the biopsy-based North American NEPTUNE cohort.\n <\/jats:p>\n \n Methods<\/jats:bold>\n We performed three ancestry-matched, genome-wide association studies (GWAS) in 273 children with NS (Children Cohort Nephrosis and Virus [NEPHROVIR] cohort: 132 European, 56 African, and 85 Maghrebian) followed by independent replication in 112 European children, transethnic meta-analysis, and conditional analysis. GWAS alleles were used to perform glomerular\n cis<\/jats:italic>\n -expression quantitative trait loci studies in 39 children in the NEPTUNE cohort and epidemiologic studies in GWAS and NEPTUNE (97 children) cohorts.\n <\/jats:p>\n \n Results<\/jats:bold>\n Transethnic meta-analysis identified one SSNS-associated single-nucleotide polymorphism (SNP) rs1063348 in the 3\u2032 untranslated region of\n HLA-DQB1<\/jats:italic>\n (\n P<\/jats:italic>\n =9.3\u00d710\n \u221223<\/jats:sup>\n ). Conditional analysis identified two additional independent risk alleles upstream of\n HLA-DRB1<\/jats:italic>\n (rs28366266,\n P<\/jats:italic>\n =3.7\u00d710\n \u221211<\/jats:sup>\n ) and in the 3\u2032 untranslated region of\n BTNL2<\/jats:italic>\n (rs9348883,\n P<\/jats:italic>\n =9.4\u00d710\n \u22127<\/jats:sup>\n ) within introns of\n HCG23<\/jats:italic>\n and\n LOC101929163<\/jats:italic>\n . These three risk alleles were independent of the risk haplotype\n DRB1*07:01-DQA1*02:01-DQB1*02:02<\/jats:italic>\n identified in European patients. Increased burden of risk alleles across independent loci was associated with higher odds of SSNS. Increased burden of risk alleles across independent loci was associated with higher odds of SSNS, with younger age of onset across all cohorts, and with increased odds of complete remission across histologies in NEPTUNE children. rs1063348 associated with decreased glomerular expression of HLA-DRB1, HLA-DRB5, and HLA-DQB1.\n <\/jats:p>\n \n Conclusions<\/jats:bold>\n Transethnic GWAS empowered discovery of three independent risk SNPs for pediatric SSNS. Characterization of these SNPs provide an entry for understanding immune dysregulation in NS and introducing a genomically defined classification.\n <\/jats:p>","DOI":"10.1681\/asn.2017111185","type":"journal-article","created":{"date-parts":[[2018,6,14]],"date-time":"2018-06-14T09:55:21Z","timestamp":1528970121000},"page":"2000-2013","source":"Crossref","is-referenced-by-count":89,"title":["Transethnic, Genome-Wide Analysis Reveals Immune-Related Risk Alleles and Phenotypic Correlates in Pediatric Steroid-Sensitive Nephrotic Syndrome"],"prefix":"10.1681","volume":"29","author":[{"given":"Hanna","family":"Debiec","sequence":"first","affiliation":[{"name":"Sorbonne Universit\u00e9, UPMC Paris 06, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Unit\u00e9 Mixte de Recherche S 1155, Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Dossier","sequence":"additional","affiliation":[{"name":"Department of Paediatric Nephrology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Letouz\u00e9","sequence":"additional","affiliation":[{"name":"Pediatric Pharmacology and Pharmacogenetics, CIC1426, H\u00f4pital Robert Debr\u00e9, Paris, France;"},{"name":"Universit\u00e9 Paris Diderot, Institut Universitaire d\u2019H\u00e9matologie, Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher E.","family":"Gillies","sequence":"additional","affiliation":[{"name":"Pediatric Nephrology, University of Michigan School of Medicine, Ann Arbor, Michigan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Vivarelli","sequence":"additional","affiliation":[{"name":"Nephrology and Dialysis Department, Istituto di Ricovero e Cura a Carattere Scientifico Ospedale Pediatrico Bambino Ges\u00f9, Rome, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosemary K.","family":"Putler","sequence":"additional","affiliation":[{"name":"Pediatric Nephrology, University of Michigan School of Medicine, Ann Arbor, Michigan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabet","family":"Ars","sequence":"additional","affiliation":[{"name":"Molecular Biology Laboratory, Fundaci\u00f3 Puigvert, Instituto de Investigaciones Biom\u00e9dicas Sant Pau, Universitat Aut\u00f2noma de Barcelona, Barcelona, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelyne","family":"Jacqz-Aigrain","sequence":"additional","affiliation":[{"name":"Pediatric Pharmacology and Pharmacogenetics, CIC1426, H\u00f4pital Robert Debr\u00e9, Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valery","family":"Elie","sequence":"additional","affiliation":[{"name":"Pediatric Pharmacology and Pharmacogenetics, CIC1426, H\u00f4pital Robert Debr\u00e9, Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Colucci","sequence":"additional","affiliation":[{"name":"Nephrology and Dialysis Department, Istituto di Ricovero e Cura a Carattere Scientifico Ospedale Pediatrico Bambino Ges\u00f9, Rome, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phanie","family":"Debette","sequence":"additional","affiliation":[{"name":"University of Bordeaux, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Bordeaux Population Health Research Center, Unit\u00e9 Mixte de Recherche 1219, CHU Bordeaux, Bordeaux, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Amouyel","sequence":"additional","affiliation":[{"name":"University of Lille, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, CHU Lille, Institut Pasteur de Lille, U1167 RID-AGE, Lille, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siham C.","family":"Elalaoui","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Institut National d\u2019Hygi\u00e8ne, Rabat, Morocco;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdelaziz","family":"Sefiani","sequence":"additional","affiliation":[{"name":"Human Genomic Center, Facult\u00e9 de M\u00e9decine et de Pharmacie Rabat, Universit\u00e9 Mohamed V. 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